This project is concerned with cardiac membrane currents and their regulation by key drugs such as catecholamines, digitalis, and local anesthetics. The rapid sodium current will be measured using rabbit Purkinje fiber preparations and two- or three-microelectrode voltage clamp techniques. We will study the inhibitory effect of tetrodotoxin, and its possible sensitivity to membrane potential. The slow inward calcium current will be investigated in ferret papillary muscles in the single sucrose gap. We will explore the effect of ouabain in increasing the slow inward current while augmenting twitch force. Measurements of intracellular ion activities of calcium and sodium will be attempted, using microelectrodes filled with neutral-carrier ion exchange resins.